Higher cardiorespiratory fitness was associated with better cognitive performance, a relationship broadly mediated by systemic inflammation (IL-6) and domain-specifically by insulin resistance.
Cross-Sectional (n=648)
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Do peripheral biological pathways including inflammation, insulin resistance, and arterial stiffness mediate the association between cardiorespiratory fitness and cognitive function in older adults?
Low-grade systemic inflammation and insulin resistance partially explain the positive association between cardiorespiratory fitness and cognitive function in older adults.
Objectives This study examined whether peripheral biological pathways including inflammation, insulin resistance, and arterial stiffness, partially explain the link between cardiorespiratory fitness (CRF) and cognitive function in older adults. Methods In a cross-sectional sample of cognitively unimpaired older adults (N = 648, 71% female, M age = 69.88 ± 3.75 years), participants completed a comprehensive cognitive battery assessing executive function (EF)/Attentional control, episodic memory, processing speed, working memory, and visuospatial abilities. CRF was measured using a maximal graded exercise test performed on a motorized treadmill. Peripheral biomarkers included low-grade systemic inflammation (Interleukin-6; IL-6), insulin resistance (Homeostatic Model Assessment for Insulin Resistance; HOMA-IR) and arterial stiffness (carotid-femoral pulse wave velocity; cfPWV). Parallel mediation models, adjusted for age, sex, study site and body fat percentage, tested whether these biomarkers statistically mediated associations between CRF and cognitive performance. Results IL-6 emerged as a consistent significant mediator of the relationship between CRF and EF, episodic memory, visuospatial processing and working memory. HOMA-IR statistically mediated the association between CRF and both EF and processing speed. In contrast, cfPWV did not statistically mediate an association between CRF and performance in any cognitive domain. Conclusion These findings suggest that low-grade systemic inflammation broadly mediates the relationship between CRF and cognitive function, while metabolic pathways show more domain-specific associations. Together, these results highlight the need for understanding the plural, yet distinct, biological mechanisms by which higher CRF relates to better cognitive performance, with the goal of identifying potential targets for interventions aimed at preserving cognitive health in older adulthood.
Solis‐Urra et al. (Mon,) conducted a cross-sectional in Cognitively unimpaired older adults (n=648). Cardiorespiratory fitness was evaluated on Cognitive performance mediated by peripheral biomarkers (IL-6, HOMA-IR, cfPWV). Higher cardiorespiratory fitness was associated with better cognitive performance, a relationship broadly mediated by systemic inflammation (IL-6) and domain-specifically by insulin resistance.